Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and peria Show more
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and periarticular manifestations, RA is also a systematic disease associated with organ-specific extra-articular manifestation. Increasing evidence indicates that RA patients are susceptible to diabetes mellitus (DM), and RA aggravates metabolic disordered in DM, indicating the close association between RA and DM. Many factors involved in RA stimulate insulin resistance and DM development. These factors include proinflammatory cytokines (such as TNF-α, IL-6, IL-1β), RA autoantibodies (such as rheumatoid factor, cyclic citrullinated peptide antibodies), excess RA related adipokines (such as leptin, resistin, ANGPTL4), C-creative protein, and other protein (such as TXNDC5, NLRP3, RBP4). Furthermore, commonly used RA drugs, such as conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), and glucocorticoids, provide potential benefits in improving insulin resistance and inhibiting DM development. This review discusses the mechanistic and therapeutic links between RA and DM, aiming to provide valuable information for the prevention and treatment of DM in RA patients. Show less
Most Alzheimer's disease (AD) loci have been discovered in individuals with European ancestry (EA). We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) r Show more
Most Alzheimer's disease (AD) loci have been discovered in individuals with European ancestry (EA). We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) reference genome-wide association study (GWAS) data set to identify Ashkenazi Jews ascertained in GWAS (n = 42,682), whole genome sequencing (WGS, n = 16,815), and whole exome sequencing (WES, n = 20,504) data sets. The association of AD was tested genome wide (GW) in the GWAS and WGS data sets and exome wide (EW) in all three data sets (EW). Gene-based analyses were performed using aggregated rare variants. In addition to apolipoprotein E (APOE), GW analyses (1355 cases and 1661 controls) revealed associations with TREM2 R47H (p = 9.66 × 10 Our results highlight the efficacy of founder populations for AD genetic studies. Show less
Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low Show more
Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low vitamin D levels. Although paricalcitol, a vitamin D receptor (VDR) activator, has demonstrated clinical benefits in patients with advanced kidney disease, its effect on cardiac remodeling in cardiomyopathy is unknown. This study aimed to investigate the relative effects of paricalcitol on cardiomyopathy in rats. Wistar-Kyoto rats were administered vehicle (sham control group) or isoproterenol to induce cardiomyopathy. Rats administered isoproterenol were subsequently treated with paricalcitol (experimental group) or vehicle (isoproterenol group). Picrosirius red and immunofluorescence staining were used to analyze cardiac fibrosis and hypertrophy. Immunohistochemistry staining was used to confirm the molecular mechanisms involved in isoproterenol-induced cardiomyopathy in rats. Injection of paricalcitol could reduce collagen and transforming growth factor-beta 1 (TGF-β1) levels while activating fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-23 (FGF23) without the help of Klotho, thereby reducing myocardial hypertrophy and fibrosis. As a VDR activator, paricalcitol reduces isoproterenol-induced cardiac fibrosis and hypertrophy by reducing the expression of TGF-β1 and enhancing the expression of VDR, FGFR1, and FGF23. Show less
Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity Show more
Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity in the Chinese indigenous Qingyuan partridge chicken. A cohort of 180 healthy 119-day-old chickens was subjected to a randomized assignment into three groups, identified as the control, R200, and R400 groups, with respective supplementation of 0, 200, and 400 mg/kg of rutin. The results revealed insignificance in growth performance, namely, average daily gain, average daily feed intake, and feed-to-gain ratio, across the various treatment groups ( Show less
Body conformation is the most direct production index, which can fully reflect pig growth status and is closely related to critical economic traits. In this study, we conducted a genome-wide associati Show more
Body conformation is the most direct production index, which can fully reflect pig growth status and is closely related to critical economic traits. In this study, we conducted a genome-wide association study (GWAS) on body conformation traits in a population of 1518 Duroc × (Landrace × Yorkshire) commercial pigs. These traits included body length (BL), body height (BH), chest circumference (CC), abdominal circumference (AC), and waist circumference (WC). Both the mixed linear model (MLM) and fixed and random model circulating probability unification (FarmCPU) approaches were employed for the analysis. Our findings revealed 60 significant single nucleotide polymorphisms (SNPs) associated with these body conformation traits in the crossbred pig population. Specifically, sixteen SNPs were significantly associated with BL, three SNPs with BH, thirteen SNPs with CC, twelve SNPs with AC, and sixteen SNPs with WC. Moreover, we identified several promising candidate genes located within the genomic regions associated with body conformation traits. These candidate genes include Show less
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunct Show more
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic beads and cultured. Western blot was used to assess NLRP3 inflammasomes. Interleukin-1β (IL-1β) and IL-18 were measured using enzyme-linked immunosorbent assay. Here we showed that the NLRP3 inflammasome was activated in non-obese diabetic (NOD) mice with SS-like manifestations. We found that NLRP3 inflammasome activation was augmented in MDSCs of SS mice and NLRP3 inflammasome activation was suppressed in IL-27-deficient NOD mice. Consistent with findings of SS mice in vivo, we observed that NLRP3 inflammasome activation by adenosine triphosphate and lipopolysaccharide was remarkably intensified in MDSCs with IL-27 treatment in vitro. Collectively, our data highlighted that IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental SS. Show less
Obesity is a global epidemic around the world. Reticulon-4B (Nogo-B) is an endoplasmic reticulum-resident protein. Our previous work demonstrated that Nogo-B deficiency inhibited obesity and decreased Show more
Obesity is a global epidemic around the world. Reticulon-4B (Nogo-B) is an endoplasmic reticulum-resident protein. Our previous work demonstrated that Nogo-B deficiency inhibited obesity and decreased the size of white adipocytes. However, the underlying molecular mechanism of Nogo-B in white adipogenesis remains poorly understood. This study aims to explore the effect of Nogo-B in white adipogenesis, as well as its underlying molecular mechanisms. The study adopted mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes to induce white adipogenesis and investigate the effect of Nogo-B on adipogenesis using qRT-PCR, Western blotting, immunofluorescence, lipid quantification, and Oil Red O staining. During white adipogenesis, Nogo-B expression was increased accompanied by upregulation of adipogenic markers. In contrast, Nogo-B deficiency inhibited white adipocyte markers expression and lipid accumulation. Furthermore, the mechanism study showed that Nogo-B deficiency decreased the destruction complex [AXIN1-APC-glycogen synthase kinase 3β (GSK3β)] levels through activating protein kinase B 2 (AKT2), resulting in β-catenin translocating into the nucleus and inhibiting the expression of adipogenic markers. Moreover, Nogo-B deficiency promoted the expression of brown/beige adipocytes markers while improving mitochondrial thermogenesis by activating β-catenin pathway. In addition, Nogo-B deficiency reduced the levels of inflammatory molecules during white adipogenic differentiation. This study revealed that Nogo-B deficiency inhibited white adipogenesis through AKT2/GSK3β/β-catenin pathway. Meanwhile, Nogo-B deficiency increased the expression of brown/beige adipocyte markers and promoted mitochondrial thermogenesis. In addition, Nogo-B deficiency reduced inflammatory cytokine levels caused by adipogenesis. Collectively, blocking Nogo-B expression may be a potential strategy to suppress white adipogenesis. Show less
Vascular dementia (VD), associated with cerebrovascular injury, is characterized by severe cognitive impairment. Jianpi Tianjing Decoction (JTD) has been widely used to treat VD. However, its molecula Show more
Vascular dementia (VD), associated with cerebrovascular injury, is characterized by severe cognitive impairment. Jianpi Tianjing Decoction (JTD) has been widely used to treat VD. However, its molecular targets and mechanisms of action in this treatment remain unclear. This study integrated network pharmacology and proteomics to identify targets and mechanisms of JTD in the treatment of VD and to provide new insights and goals for clinical treatments. Systematic network pharmacology was used to identify active chemical compositions, potential targets, and mechanisms of JTD in VD treatment. Then, a mouse model of VD was induced via transient bilateral common carotid artery occlusion to verify the identified targets and mechanisms of JTD against VD using 4D label-free quantitative proteomics. By screening active chemical compositions and potential targets in relevant databases, 187 active chemical compositions and 416 disease-related compound targets were identified. JTD may suppress VD development via multiple components, targets, and pathways. It may thus serve as a complementary treatment option for patients with VD. Show less
Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has grad Show more
Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression. The tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction. The results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m Our study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology. Show less
Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed t Show more
Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed to identify proteomic signatures and pathways related to these risk loci to better characterize AAA genetic susceptibility. Plasma concentrations of 4870 proteins were determined using a DNA aptamer-based array. Linear regression analysis estimated the associations between the 23 risk alleles and plasma protein levels with adjustments for potential confounders in a race-stratified analysis of 1671 Black and 7241 White participants. Significant proteins were then evaluated for their prediction of clinical AAA (454 AAA events in 11 064 individuals), and those significantly associated with AAA were further interrogated using Mendelian randomization analysis. Risk variants proximal to Low levels of neogenin and kit ligand may be novel risk factors for AAA development in potentially causal pathways. These findings provide insights and potential targets to reduce AAA susceptibility. Show less
Despite the widespread use of statins, newer lipid-lowering drugs have been emerging. It remains unclear how the long-term use of novel lipid-lowering drugs affects the occurrence of cancers and age-r Show more
Despite the widespread use of statins, newer lipid-lowering drugs have been emerging. It remains unclear how the long-term use of novel lipid-lowering drugs affects the occurrence of cancers and age-related diseases. A drug-target Mendelian randomization study was performed. Genetic variants of nine lipid-lowering drug-target genes ( In addition to marked effects on decreased risks of atherosclerotic cardiovascular diseases, genetically proxied lipid-lowering variants of Our study provides genetic evidence that newer nonstatin lipid-lowering agents have causal effects on decreased risks of several common cancers and cardiometabolic diseases. These data provide genetic insights into the potential benefits of newer nonstatin therapies. Show less
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors Show more
Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors at the time of diagnosis, especially lymph node metastasis (LNM). This study aimed to construct a LNM-related gene signature for predicting the prognosis of patients with LUAD. RNA sequencing data and clinical information of LUAD patients were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Samples were divided into metastasis (M) and nonmetastasis (NM) groups based on LNM status. Differentially expressed genes (DEGs) between M and NM groups were screened, and then WGCNA was applied to identify key genes. Furthermore, univariate Cox and LASSO regression analyses were conducted to construct a risk score model, and the predictive performance of model was validated by GSE68465, GSE42127, and GSE50081. The protein and mRNA expression level of LNM-associated genes were detected by human protein atlas (HPA) and GSE68465. A prognostic model based on eight LNM-related genes (ANGPTL4, BARX2, GPR98, KRT6A, PTPRH, RGS20, TCN1, and TNS4) was developed. Patients in the high-risk group had poorer overall survival than those in the low-risk group, and validation analysis showed that this model had potential predictive value for patients with LUAD. HPA analysis supported the upregulation of ANGPTL4, KRT6A, BARX2, RGS20 and the downregulation of GPR98 in LUAD compared with normal tissues. Our results indicated that the eight LNM-related genes signature had potential value in the prognosis of patients with LUAD, which may have important practical implications. Show less
Linping Wang, Jingqi Zhang, Yue Zhao+5 more · 2023 · Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · Elsevier · added 2026-04-24
Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, β-secretase (BACE1), and amy Show more
Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, β-secretase (BACE1), and amyloid beta (Aβ) in vivo and in vitro. Previous studies by our research group have shown that this is partly caused by the negative regulation of BACE1 by miRNA29a/b1 (miR29a/b1). Despite the observed the role of nuclear factor kappa B (NF-κB) on many miRNAs, the upstream regulation of NF-κB protein on miR29 remains poorly understood. The purpose of this study was to better define the relationship between NF-κB and miR29a/b1 and the potentially relevant signaling pathways. On the one hand, we constructed the animal model of Al exposure by the intraperitoneal injection of aluminum-maltolate (Al(mal) We verified that NF-κB shows an increasing trend with Al accumulation in the brain of rats, which is accompanied by a downward trend of miR29a/b1. Notably, the suppression of NF-κB significantly increased miR29a/b1 and affected the expression of BACE1mRNA and downstream proteins. Al-induced NF-κB can negatively regulate the expression of miR29a/b1, which then significantly enhances the expression of BACE1 and Aβ plaques. Show less
The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state accor Show more
The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Show less
Chicken is considered an ideal model species to study the synthesis of polyunsaturated fatty acids (PUFAs) due to its appropriate proportions of fatty acids and abundant content of PUFAs, suitable for Show more
Chicken is considered an ideal model species to study the synthesis of polyunsaturated fatty acids (PUFAs) due to its appropriate proportions of fatty acids and abundant content of PUFAs, suitable for human consumption. However, the molecular mechanisms regulating poultry PUFA synthesis remain unclear. Here, we systematically explored the transcriptional regulation activity of the gene family related to PUFA synthesis in chicken by carrying out the Dual-Luciferase Reporter Assay. We identified the core promoter regions of members of the chicken PUFA synthesis-related gene family, including ELOVL1, ELOVL2, ELOVL3, ELOVL4, ELOVL5, ELOVL6, ELOVL7, FADS1, FADS2, FADS6, SCD, and SCD5. Additionally, changes in relative fluorescence values of different truncated segments in the upstream regulatory region of these genes indicate the existence of regulatory regions. Furthermore, we predicted the transcription factors that bind to the identified core promoter regions of multiple genes, including Sp1, NF-1, C/EBPalpha, etc. These findings provide a basis for the molecular mechanisms regulating poultry PUFA synthesis and offer new scientific insight into the potential improvement of poultry meat quality in the future. Show less
Goat milk is increasingly recognized by consumers due to its high nutritional value, richness in short- and medium-chain fatty acids, and richness in polyunsaturated fatty acids (PUFA). Exogenous supp Show more
Goat milk is increasingly recognized by consumers due to its high nutritional value, richness in short- and medium-chain fatty acids, and richness in polyunsaturated fatty acids (PUFA). Exogenous supplementation of docosahexaenoic acid (DHA) is an important approach to increasing the content of PUFA in goat milk. Several studies have reported benefits of dietary DHA in terms of human health, including potential against chronic diseases and tumors. However, the mechanisms whereby an increased supply of DHA regulates mammary cell function is unknown. In this study, we investigated the effect of DHA on lipid metabolism processes in goat mammary epithelial cells (GMEC) and the function of H3K9ac epigenetic modifications in this process. Supplementation of DHA promoted lipid droplet accumulation increased the DHA content and altered fatty acid composition in GMEC. Lipid metabolism processes were altered by DHA supplementation through transcriptional programs in GMEC. ChIP-seq analysis revealed that DHA induced genome-wide H3K9ac epigenetic changes in GMEC. Multiomics analyses (H3K9ac genome-wide screening and RNA-seq) revealed that DHA-induced expression of lipid metabolism genes ( Show less
Qi Jiang, Ruolan Miao, Yuhuan Wang+8 more · 2023 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ov Show more
Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS. Show less
Hand, foot, and mouth disease (HFMD) is a common viral childhood illness caused most commonly by enterovirus 71 (EV71) and coxsackievirus A16. The pathogenesis of EV71 has been extensively studied, an Show more
Hand, foot, and mouth disease (HFMD) is a common viral childhood illness caused most commonly by enterovirus 71 (EV71) and coxsackievirus A16. The pathogenesis of EV71 has been extensively studied, and the regulation of the host immune response is suspected to aggravate the serious complications induced by EV71. Our previous research showed that EV71 infection significantly increased the release of circulating interleukin (IL)-6, IL-10, IL-13, and IL-27. Notably, these cytokines are related to the EV71 infection risk and clinical stage. Polyamines are compounds that are ubiquitous in mammalian cells and play a key role in various cellular processes. Several studies have shown that targeting polyamine metabolic pathways can reduce infections caused by viruses. However, the significance of polyamine metabolism in EV71 infection remains largely unknown. Serum samples from 82 children with HFMD and 70 healthy volunteers (HVs) were collected to determine the polyamine metabolites spermidine (SPD) and spermine (SPM), and IL-6 levels. In addition, peripheral blood mononuclear cells (PBMCs) were treated with EV71 viral protein 1 (VP1) and EV71 VP4, and the cells and supernatant were then collected to analyze the expression of polyamine metabolism-related enzymes by western blot. The data were analyzed using GraphPad Prism 7.0 software (USA). The serum polyamine metabolites SPD and SPM were elevated in the HFMD patients, especially in the EV71-infected children. Further, a positive correlation was found between serum SPD and IL-6 levels in the EV71-infected children. We also found that the upregulation of peripheral blood polyamine metabolites in the EV71-infected HFMD children was related to EV71 capsid protein VP1, but not VP4. VP1 may promote the expression of polyamine metabolism-related enzymes and promote the production of polyamine metabolites, thereby upregulating the SPD/nuclear factor kappa B/IL-6 signaling pathway. However, VP4 has the opposite effect in this process. Our results suggest that EV71 capsid protein may regulate the polyamine metabolic pathways of infected cells in a variety of ways. This study provides insights into the mechanism of EV71 infection and polyamine metabolism and has good reference value for the development of EV71 vaccine. Show less
TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we inv Show more
TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of β-secretase (BACE1) and C99, as well as Aβ peptides (including Aβ40 and Aβ42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1. Show less
This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN). EXT1 was detected in 67 renal tissues of M-type phospholi Show more
This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN). EXT1 was detected in 67 renal tissues of M-type phospholipase A2 receptor (PLA2R)-negative and ANA-positive membranous nephropathy by immunohistochemistry, and cases were divided into confirmed LMN and suspected LMN. The clinicopathological data were compared among the above groups, as well as EXT1-positive group and EXT1-negative group. Twenty-two cases (73.3%) of confirmed LMN and six cases (16.2%) of suspected LMN exhibited EXT1 expression on the glomerular basement membrane and/or mesangium area, showing a significant difference (p<0.001). Concurrently, lupus nephritis (LN) of pure class V demonstrated a lower frequency of EXT1 positivity compared with mixed class V LN in the confirmed LMN group (31.8% vs 68.2%, p=0.007). EXT1-positive patients in the confirmed and suspected LMN group showed significant differences in some clinicopathological data comparing with EXT1-negative patients (p<0.05). Follow-up data revealed that a greater proportion of patients in the EXT1-positive group achieved complete remission post-treatment (p<0.05). Cox regression analysis showed that EXT1 positivity was significantly correlated with complete remission across the entire study cohort (HR 5.647; 95% CI, 1.323 to 12.048; p=0.019). Kaplan-Meier analysis indicated that the EXT1-positive group had a higher rate of accumulated nephrotic remission compared with the EXT1-negative group in the whole study cohort (p=0.028). The EXT1-positive group exhibited a higher active index and a more favourable renal outcome than the EXT1-negative group. It would be better to recognise suspected LMN with EXT1 positivity as a potential autoimmune disease and maintain close follow-up due to its similarities with confirmed LMN. Show less
The decreased osteogenic differentiation ability of mesenchymal stem cells (MSCs) is one of the important reasons for SOP. Inhibition of Wnt signaling in MSCs is closely related to SOP. Microtubule ac Show more
The decreased osteogenic differentiation ability of mesenchymal stem cells (MSCs) is one of the important reasons for SOP. Inhibition of Wnt signaling in MSCs is closely related to SOP. Microtubule actin crosslinking factor 1 (MACF1) is an important regulator in Wnt/β-catenin signal transduction. However, whether the specific expression of MACF1 in MSC regulates SOP and its mechanism remains unclear. We established MSC-specific Prrx1 (Prx1) promoter-driven MACF1 conditional knock-in (MACF-KI) mice, naturally aged male mice, and ovariectomized female mice models. Micro-CT, H&E staining, double calcein labeling, and the three-point bending test were used to explore the effects of MACF1 on bone formation and bone microstructure in the SOP mice model. Bioinformatics analysis, ChIP-PCR, qPCR, and ALP staining were used to explore the effects and mechanisms of MACF1 on MSCs' osteogenic differentiation. Microarray analysis revealed that the expression of MACF1 and positive regulators of the Wnt pathway (such as TCF4, β-catenin, Dvl) was decreased in human MSCs (hMSCs) isolated from aged osteoporotic than non-osteoporotic patients. The ALP activity and osteogenesis marker genes (Alp, Runx2, and Bglap) expression in mouse MSCs was downregulated during aging. Furthermore, Micro-CT analysis of the femur from 2-month-old MSC-specific Prrx1 (Prx1) promoter-driven MACF1 conditional knock-in (MACF-cKI) mice showed no significant trabecular bone changes compared to wild-type littermate controls, whereas 18- and 21-month-old MACF1 c-KI animals displayed increased bone mineral densities (BMD), improved bone microstructure, and increased maximum compression stress. In addition, the ovariectomy (OVX)-induced osteoporosis model of MACF1 c-KI mice had significantly higher trabecular volume and number, and increased bone formation rate than that in control mice. Mechanistically, ChIP-PCR showed that TCF4 could bind to the promoter region of the host gene miR-335-5p. Moreover, MACF1 could regulate the expression of miR-335-5p by TCF4 during the osteogenic differentiation of MSCs. These data indicate that MACF1 positively regulates MSCs osteogenesis and bone formation through the TCF4/miR-335-5p signaling pathway in SOP, suggesting that targeting MACF1 may be a novel therapeutic approach against SOP. MACF1, an important switch in the Wnt signaling pathway, can alleviate SOP through the TCF4/miR-335-5p signaling pathway in mice model. It might act as a therapeutic target for the treatment of SOP to improve bone function. Show less
Locally advanced and metastatic pancreatic cancer (PC) frequently grows in adipose tissue and has a poor prognosis. Although adipose tissue is largely composed of adipocytes, the mechanisms by which a Show more
Locally advanced and metastatic pancreatic cancer (PC) frequently grows in adipose tissue and has a poor prognosis. Although adipose tissue is largely composed of adipocytes, the mechanisms by which adipocytes impact PC are poorly understood. Using an Show less
Atabecestat, a potent brain penetrable BACE1 inhibitor that reduces CSF amyloid beta (Aβ), was developed as an oral treatment for Alzheimer's disease (AD). Elevated liver enzyme adverse events were re Show more
Atabecestat, a potent brain penetrable BACE1 inhibitor that reduces CSF amyloid beta (Aβ), was developed as an oral treatment for Alzheimer's disease (AD). Elevated liver enzyme adverse events were reported in three studies although only one case met Hy's law criteria to predict serious hepatotoxicity. We performed a case-control genome-wide association study (GWAS) to identify genetic risk variants associated with liver enzyme elevation using 42 cases with alanine transaminase (ALT) above three times the upper limit of normal (ULN) and 141 controls below ULN. Additionally, we performed a GWAS using continuous maximal ALT/ULN (expressed as times the ULN) upon exposure to atabecestat as the outcome measure (n = 285). No variant passed the genome-wide significance threshold (p = 5 × 10 The suggestive GWAS signals in the case-control GWAS analysis suggest the potential role of inflammation in atabecestat-induced liver enzyme elevation. Show less
Channel catfish, Ictalurus punctatus, have limited ability to synthesize Ω-3 fatty acids. The ccβA-msElovl2 transgene containing masu salmon, Oncorhynchus masou, elongase gene driven by the common car Show more
Channel catfish, Ictalurus punctatus, have limited ability to synthesize Ω-3 fatty acids. The ccβA-msElovl2 transgene containing masu salmon, Oncorhynchus masou, elongase gene driven by the common carp, Cyprinus carpio, β-actin promoter was inserted into the channel catfish melanocortin-4 receptor (mc4r) gene site using the two-hit two-oligo with plasmid (2H2OP) method. The best performing sgRNA resulted in a knockout mutation rate of 92%, a knock-in rate of 54% and a simultaneous knockout/knock-in rate of 49%. Fish containing both the ccβA-msElovl2 transgene knock-in and mc4r knockout (Elovl2) were 41.8% larger than controls at 6 months post-hatch (p = 0.005). Mean eicosapentaenoic acid (EPA, C20:5n-3) levels in Elov2 mutants and mc4r knockout mutants (MC4R) were 121.6% and 94.1% higher than in controls, respectively (p = 0.045; p = 0.025). Observed mean docosahexaenoic acid (DHA, C22:6n-3) and total EPA + DHA content was 32.8% and 45.1% higher, respectively, in Elovl2 transgenic channel catfish than controls (p = 0.368; p = 0.025). To our knowledge this is the first example of genome engineering to simultaneously target transgenesis and knock-out a gene in a commercially important aquaculture species for multiple improved performance traits. With a high transgene integration rate, improved growth, and higher omega-3 fatty acid content, the use of Elovl2 transgenic channel catfish appears beneficial for application on commercial farms. Show less
Kidney cancer undergoes a dramatic metabolic shift and has demonstrated responsiveness to immunotherapeutic intervention. However, metabolic classification and the associations between metabolic alter Show more
Kidney cancer undergoes a dramatic metabolic shift and has demonstrated responsiveness to immunotherapeutic intervention. However, metabolic classification and the associations between metabolic alterations and immune infiltration in Renal cell carcinoma still remain elucidative. Unsupervised consensus clustering was conducted on the TCGA cohorts for metabolic classification. GESA, mRNAsi, prognosis, clinical features, mutation load, immune infiltration and differentially expressed gene differences among different clusters were compared. The prognosis model and nomograms were constructed based on metabolic gene signatures and verified using external ICGC datasets. Immunohistochemical results from Human Protein Atlas database and Tongji hospital were used to validate gene expression levels in normal tissues and tumor samples. CCK8, apoptosis analysis, qPCR, subcutaneously implanted murine models and flowcytometry analysis were applied to investigate the roles of ACAA2 in tumor progression and anti-tumor immunity. Renal cell carcinoma was classified into 3 metabolic subclusters and the subcluster with low metabolic profiles displayed the poorest prognosis, highest invasiveness and AJCC grade, enhanced immune infiltration but suppressive immunophenotypes. ACAA2, ACAT1, ASRGL1, AKR1B10, ABCC2, ANGPTL4 were identified to construct the 6 gene-signature prognosis model and verified both internally and externally with ICGC cohorts. ACAA2 was demonstrated as a tumor suppressor and was associated with higher immune infiltration and elevated PD-1 expression of CD8 Our research proposed a new metabolic classification method for RCC and revealed intrinsic associations between metabolic phenotypes and immune profiles. The identified gene signatures might serve as key factors bridging tumor metabolism and tumor immunity and warrant further in-depth investigations. Show less
Arabidopsis nucleoporin involved in the regulation of ethylene signaling via controlling of nucleocytoplasmic transport of mRNAs. The two-way transport of mRNAs between the nucleus and cytoplasm are c Show more
Arabidopsis nucleoporin involved in the regulation of ethylene signaling via controlling of nucleocytoplasmic transport of mRNAs. The two-way transport of mRNAs between the nucleus and cytoplasm are controlled by the nuclear pore complex (NPC). In higher plants, the NPC contains at least 30 nucleoporins. The Arabidopsis nucleoporins are involved in various biological processes such as pathogen interaction, nodulation, cold response, flowering, and hormone signaling. However, little is known about the regulatory functions of the nucleoporin NUP160 and NUP96 in ethylene signaling pathway. In the present study, we provided data showing that the Arabidopsis nucleoporin NUP160 and NUP96 participate in ethylene signaling-related mRNAs nucleocytoplasmic transport. The Arabidopsis nucleoporin mutants (nup160, nup96-1, nup96-2) exhibited enhanced ethylene sensitivity. Nuclear qRT-PCR analysis and poly(A)-mRNA in situ hybridization showed that the nucleoporin mutants affected the nucleocytoplasmic transport of all the examined mRNAs, including the ethylene signaling-related mRNAs such as ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, and EIN3. Transcriptome analysis of the nucleoporin mutants provided clues suggesting that the nucleoporin NUP160 and NUP96 may participate in ethylene signaling via various molecular mechanisms. These observations significantly advance our understanding of the regulatory mechanisms of nucleoporin proteins in ethylene signaling and ethylene response. Show less
Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summa Show more
Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aβ via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD. Show less
Human papillomavirus belongs to papovaviridae family papillomavirus A, a spherical deoxyribonucleic acid (DNA) virus, which can cause the proliferation of squamous epithelial cells of human skin or mu Show more
Human papillomavirus belongs to papovaviridae family papillomavirus A, a spherical deoxyribonucleic acid (DNA) virus, which can cause the proliferation of squamous epithelial cells of human skin or mucous membranes. With the rapid increase in the incidence of condyloma acuminatum among STDs and the increase in diseases caused by HPV infection, HPV infection has seriously endangered human health. In this paper, the in vitro detection of HPV E1 protein was realized using AgNCs-dsDNA. And through the test of this detection method, we calculated that the detection limit of this method is 0.886 nM. Compared with other methods for detecting E1 protein in vitro, this method has high sensitivity and simple operation. In addition, the detection method also has good anti-interference and selectivity, and can realize the detection of E1 in serum samples. The transfection efficiency of BLV-miR-B4-3p mimics at different time points was determined by quantitative real-time PCR (qPCR); the transcriptome sequencing of lymphocytes transfected with different concentrations of BLV-miR-B4-3p mimics was performed, and differential gene clustering was performed on the sequencing results. And the BLV-miR-B4-3p target gene prediction and transcriptome analysis results were verified by qPCR. The effects of BLV-miR-B4-3p on the transcriptional levels of immune-related cytokines in human lymphocytes were analyzed. Transcriptome sequencing analysis showed that after BLV-miR-B4-3p entered lymphocytes, a total of 556 differentially expressed genes were obtained. GO enrichment and KEGG analysis results showed that BLV-miR-B4-3p could independently activate influenza. The signaling pathway ultimately affects the body's immune system process, stress response, defense response, immune response, and other biological processes. After BLV-miR-B4-3p enters lymphocytes, it will lead to abnormal lymphocyte immune function, including the mRNA expression of TNF-α in Th1 cytokines which was significantly increased (P < 0.05), and the expression of IL-10 in Th2 cytokines was significantly increased (P < 0.05). The mRNA expression was significantly decreased (P < 0.05), and the mRNA expression of IL-27 was significantly increased (P < 0.001), which did not affect the mRNA expression of lymphocyte proliferation and activation-related regulators. The tumor suppressor breast cancer 1 (BRCA1) and antimicrobial peptide CAMP were significantly increased, and decreased (P < 0.001), and the expression of pro-apoptotic factor Caspase9 showed a significant downward trend (P < 0.05). Show less